Wednesday, May 29, 2013

Been reading some somewhat old material out there on women in academia. I am getting more and more interested in this issue especially as I have become more involved in the UC Davis ADVANCE Program. The ADVANCE program from the National Science Foundation "aims to increase the participation and advancement of women in academic science and engineering careers."

“The process itself is pretty much a replication of the processes used in microbiology to cultivate bacteria on agar in petri dishes,” Raitenan says. “Instead of agar, I just used the film gelatin as my growth medium. As the bacteria grows, it consumes the gelatin layers that together make all the colors in a color photograph, and creates all these random patterns and colors.”

Plus - of course - there is a continuous stream of information on microbes from Carl Zimmer who writes frequently for the NY Times. Perhaps the best example of this is his coverage of the Human Microbiome Project papers: Studies of Human Microbiome Yield New Insights June 18, 2012. But there have been and I am sure will be others.

Sure - the NY Times is not the only place with a bunch of stories about microbial diversity and microbiomes. But they do seem tto have a good ratio of "diversity" themed coverage vs. germoophobia themed topics which are common in many other places.

Well, this is one of the bigger screw ups in terms of evolution I have seen at a major journal in a while. See the following paper in Nature: The catalytic mechanism for aerobic formation of methane by bacteria : Nature. The paper discusses some functions of "the ocean-dwelling bacterium Nitrosopumilus maritimus." Some of what is reported in the paper is perhaps interesting (alas I do not have access). But painfully, there is one big big big big mistake - you see Nitrosopumilus maritimus is not a bacterium. It is an archaeon (see for example this paper on its genome).

I got pointed to this by Uri Gophna (in an email and in a comment on my blog)(all see this on Twitter) Sure - some people debate the structure of the tree of life. But I am pretty certain the authors here (Siddhesh S. Kamat, Howard J. Williams, Lawrence J. Dangott, Mrinmoy Chakrabarti & Frank M. Raushel) are not trying to make a statement about monophyly of bacteria or just what archaea are. They just made what seems to be a colossal screw up. And Nature not only let them, but added to it with things like their "Editors Summary":

Novel bacterial biosynthesis of methane
Aerobic marine organisms produce significant quantities of the potent greenhouse gas methane, much of it via the cleavage of the highly unreactive carbon–phosphorus bonds of alkylphosphonates. In this study the authors explore the mechanism of PhnJ, an unusual radical S-adenosyl-L-methionine (SAM) enzyme that appears to use a cysteine-based thiyl radical to help catalyse the conversion of the alkylphosphonate substrate to methane and ribose-1,2-cyclic phosphate-5-phosphate. This reaction, not previously encountered in biological chemistry, establishes a novel mechanism for cleaving carbon–phosphorus bonds to form methane and phosphate via a covalent thiophosphate intermediate.

And for this taxonomic alchemy (converting an archaeon to a bacterium) I am awarding them and Nature my coveted "Twisted Tree of Life Award #16".

UPDATE 5/28 7AM

I love the ad that came up while I was writing this post and searching for some information. I think Nature could use the services from this ad:

Thanks to Michael Ferrari for pointing me to this:: Mobile Robotic Laboratory Will Track Ocean Toxins - Popular Mechanics. The article discusses some developments at MBARI for mobile sensor / sampler devices that could be used for various marine microbiology studies. A few years ago I got a tour of MBARI from Alex Worden (see pics below) and got to see some of their toys but many of the developments in this article are new to me. I can't wait until it is possible to deploy a few hundred thousand of these and get massive amounts of data ...

Sunday, May 26, 2013

I attended the American Society for Microbiology (ASM) meeting in Denver last week. It was a bit overwhelming as usual, with the 1000s of people there. One surprise for me was an invitation to a after dinner party hosted by Nathan Wolfe and others from Metabiota. I am not really a big fan of parties (as many who know me know) but this was small and even better it was mostly populated by the recipients of the ASM International Young Ambassador Award winners. Wolfe was one of the keynote speakers at the ASM Meeting and I think he was hosting this party in part as a reception for the Young Ambassador's.

Abstract:
The PhyloFacts ‘Fast Approximate Tree Classification’ (FAT-CAT) web server provides a novel approach to ortholog identification using subtree hidden Markov model-based placement of protein sequences to phylogenomic orthology groups in the PhyloFacts database. Results on a data set of microbial, plant and animal proteins demonstrate FAT-CAT’s high precision at separating orthologs and paralogs and robustness to promiscuous domains. We also present results documenting the precision of ortholog identification based on subtree hidden Markov model scoring. The FAT-CAT phylogenetic placement is used to derive a functional annotation for the query, including confidence scores and drill-down capabilities. PhyloFacts’ broad taxonomic and functional coverage, with >7.3 M proteins from across the Tree of Life, enables FAT-CAT to predict orthologs and assign function for most sequence inputs. Four pipeline parameter presets are provided to handle different sequence types, including partial sequences and proteins containing promiscuous domains; users can also modify individual parameters. PhyloFacts trees matching the query can be viewed interactively online using the PhyloScope Javascript tree viewer and are hyperlinked to various external databases. The FAT-CAT web server is available at http://phylogenomics.berkeley.edu/phylofacts/fatcat/.

Wednesday, May 22, 2013

I am pleased to have a guest post in my "Story behind the paper" series. This one is from Jeremy Barr in Forest Rohwer's lab about a new PNAS paper.

Bacteriophage and mucus. Two unlikely entities, or an exceptional symbiosis?

By Jeremy J. Barr

Our recent research at The Rohwer Lab at San Diego State University investigates a new symbiosis formed between bacteriophage, viruses that only infect and kill bacteria, and mucus, that slimy stuff coating your mouth, nose, lungs and gut.

Bacteriophage, or phage for short are ubiquitous throughout nature. They are found everywhere. So it shouldn’t surprise you to learn that these phage are also found within mucus. In fact, if you actually sat down and thought about the best place you would look for phage, you might have picked mucus as a great starting point. Mucus is loaded with bacteria, and like phage, is found everywhere. Almost every animal uses mucus, or a mucus-like substance, to protect its environmentally exposed epithelium from the surrounding environment. Phage in mucus is nothing novel.

But what if there were more phage in mucus? What if the phage, immotile though they may be, were actually sticking within it?

It turns out that there are more phage in mucus, over four times more phage, and this appears true across extremely divergent animal mucosa. But this apparent increase in phage could very simply be explained by increased replication due to access to increased bacterial hosts residing within mucus layers. But this assumption alone doesn’t hold up. Applying phage T4 to sterile tissue culture cells resulted in significantly more phage sticking to the cell lines that produced a mucus layer, compared to those that did not. There were no bacterial hosts for phage replication in these experiments. Yet still, more phage accumulated in mucus.

Surely the law of mass-action could explain this apparent accumulation. The more phage we apply to an aqueous external environment, the more phage will diffuse into and enter the mucus layer, being slowed in the process due to the gel-like properties, and eventually resulting in an apparent accumulation of phage in mucus. But when we removed mass-action from the equation, and simply coated mucus-macromolecules onto a surface, still more phage stuck. Our assumptions were too simple.
Phage are ingenious. They have evolved, traded, and disseminated biological solutions to almost every biological problem, whether we are aware of it or not. So in order to solve the phage-mucus quandary, we needed to look to one of the most ubiquitous and populous families of proteins found in nature: the immunoglobulin superfamily. This protein fold is so ubiquitous that it appears in almost every form of life. Within our own bodies, it is the protein that affords us immunological protection. Bacteria utilize the protein fold to adhere to each other, to surfaces, and as a form of communication. And as it would turn out, phage make an innovative use of the same protein fold to stick to mucus.

Immunoglobulin, phage and mucus, are all pervasive throughout environments. The interaction between these three entities forms a new symbiosis between phage and their animal hosts. This symbiosis contributes a previously unrecognized immune system that reduces bacterial numbers in mucus, and protects the animal host from attack. We call this symbiosis/immunity, Bacteriophage Adherence to Mucus, or BAM for short.

Sunday, May 19, 2013

I am sitting on a Southwest Airlines flight heading to Denver for the American Society for Microbiology 2013 meeting. At 3 PM today I am scheduled to co-chair (with David Coil from my lab) a session on “Citizen Microbiology” (well the full title is Citizen Microbiology: Enhancing Microbiology Education and Research with the Help of the Public). The schedule of the session is at the bottom of this post but it promises to be very interesting and exciting (no bias here at all).

As far as I know, this is the first session ever on “Citizen Microbiology” at a large meeting of any kind. We held a small workshop at UC Davis in January of 2012 on Citizen Microbiology but that was quite small. I note - I use a very broad definition for Citizen Microbiology including basically any project that engages the public in some way to participate in a research project relating to microbes. This is the perfect time to have such a session at a large meeting and the ASM General Meeting is an ideal setting. There are a series of converging forces that makes this timing ideal including:

There is a growing appreciation of microbes and the role they play on the planet. Some of this appreciation is broad - covering all microbes - all the time - everywhere. But much of it is due to a growing interest in the microbes closer to us - those that live in and on us (the human microbiome) - those that live in and on plants and animals and other organisms we care about - and those that live in the places where we spend much of our time (the microbes of the built environment). I mean - come on - everyone is talking about fecal transplants now in public - in cover stories of the NY Times Magazine and in Ted talks.

Technological and scientific advances have made it possible to better sample the microbes found in any particular location. Clearly, DNA sequencing technology and associated analytical tools are a central component of these advances, but other factors are important too.

The world is becoming more and more digital which makes the sharing of information (which is key to Citizen Science) easier and better. And social media has made it easier to communicate and discuss actions like Citizen Microbiology.

Crowdsourcing (not the same thing as Citizen Science - more on this another time perhaps) is also growing in leaps and bounds.

Crowdfunding is providing new ways to fund scientific activities.

Sensors of all kinds are getting cheaper and easier to use and are being deployed widely.

Many people are becoming more and more interesting in recording information about themselves and sharing it with others.

The “open science” movement is making the literature, software, methods and data and more available to everyone with no or few restrictions thus allowing for more people in diverse environments to become engaged in research.

We have done, and continue to do, serious harm to our microbial world. Antibiotics are overused. Antimicrobials are in everything. More and more children and missing out on vaginal birth. And so on

Although our understanding of the importance of microbes is everywhere, there are also many who are overselling what we know - claiming that probiotics will cure all ailments for example.

Some information about microbes that is out there on the web is, well, less that ideal

The ethics of engaging the public in studies of microbes are not fully appreciated by some and not completely understood by most.

So this is both an exciting and a critical time for microbes and microbiology. And I hope that this session will not only help launch the field of Citizen Microbiology, but will help get everyone to think about the bigger issues and how to move the field forward in the right directions. For there is so much we need to do and think about including

Ethics

Funding

Openness and sharing

Visualization

Analysis tools

Communication

Outreach

And of course - the people at the session are not the only ones engaged in Citizen Microbiology or related activities (see a list we made a while back here). If you are doing a project please post something about it here. And if you are not doing a Citizen Microbiology project - well - why not? Get your act together.

Anyway - got to put away the computer as we land in Denver soon and I will rush off to the conference center, hopefully on time, to chair this exciting session. And I hope to see you there or have you follow online (check out the Twitter hash tag #ASM2013). And keep your eyes open for more excitement in this area.

Quick post here. There is a really nice piece on in the New York Times Sunday Magazine by Michael Pollan on the human microbiome: Say Hello to the 100 Trillion Bacteria That Make Up Your Microbiome. In it he discusses how he had his microbiome typed by the American Gut Project and he discusses browsing through the output. He also discusses a diversity of issues in the microbiome and work of various folks. People featured include Justin Sonnenburg, Rob Knight, Burce German, Catherine Lozupone, Stanley Falkow, Jeffrey Gordon, Michael Fischback, Maria Gloria Dominguez-Bello, Martin Blaser, Ruth Ley, Andrew Gewirtz, Patrice Cani, Erica Sonnenburg, and Stephen O'Keefe. The article does a really good job of highlighting why the microbiome is important yet does not oversell what we know at this point.

I note - Pollan came to UC Davis as part of his research for the article a little while back. Below are some pics of him getting a tour of the UC Davis LEED Platinum brewing facility. Anyway the article is definitely worth a look. And just in time for the ASM 2013 Meeting which I am about to head to this AM.

I guess the FDA feels like they have to do something given the spread of FT. Given how many scam artists and oversellers of the microbiome are out there I think some sort of increased protection or regulation is probably a good thing. But I am not sure what the best way to do this is. Clearly some are unhappy with the FDA sticking their noses into fecal transplants (e.g., see here). But given how little we know about FTs other than as treatment for Clostridium dificile infections it seems like one could make a reasonable argument for more regulation or caution. It seems strange though that we can do just about anything and everything we want to kill all the microbes around us with very little regulation and yet attempting to manipulate the microbes in and on us or add a few here and there is being regulated more.

What do others think? Do we need more regulation from the FDA on fecal transplants?

Software Carpentry helps researchers be more productive by teaching them basic computing skills. We run boot camps at dozens of sites around the world, and also provide open access material online for self-paced instruction. The benefits are more reliable results and higher productivity: a day a week is common, and a ten-fold improvement isn't rare.

Tuesday, May 14, 2013

Fun. Another day. Another YAMMGM (yet another mostly male genomics meeting). This one is the International Conference on Genomics Europe 2013. I have copied the program as it is now here and then highlighted the men and women as far as I can tell. And, well, it is not very balanced. It starts off, ironically, with "Omics and the future of man" and then stays on both omics and alas, men, for most of the meeting. The first woman does not talk until 5 pm on the first day. Nothing against BGI per se. But they seem to be repeat offenders in having meetings with mostly male speakers. A difference between countries? Perhaps. But unfortunate and unpleasant nevertheless.

I know I complain all the time about news stories and people "overselling the microbiome". Mind you, I believe microbial communities are likely to be found to have very very important roles in the biology of the plants and animals and other organisms on which they live, but I worry about overhyping the possibilities. But thankfully, there are some good researchers at work out there documenting just what the microbiome can and does do. And the results continue to be promising.

Here is the one that caught my eye most recently: BBC News - 'Weight loss gut bacterium' found about this PNAS paper. While the study is in mice and it is what one could call "limited" in some ways, it is really fascinating and has much promise. Basically, they isolated a new bacterium (with the awkward name of Akkermansia muciniphila, and did a series of experiments in mice looking at the role this bacterium can play in many mouse gut properties. But most interesting, treatment of mice with this bacterium (and only when the bacterium was alive) led to a reduction in high fat induced metabolic disorders and obesity. I am still re-reading the paper but the result seems solid. And exciting.

So - there is no need to oversell the microbiome when the results coming in sell themselves ...

Brought to us by NBC News and LiveScience (which actually can have some pretty good science coverage). This article has some complete and utter crap:

Some parts that I have issues with:

The headline: "'Junk' DNA mystery solved: It's not needed." The headline is silly but alas it is consistent with what is in the article.

"So-called junk DNA, the vast majority of the genome that doesn't code for proteins". So - they have redefined junk DNA as all non coding DNA?

"For decades, scientists have known that the vast majority of the genome is made up of DNA that doesn't seem to contain genes or turn genes on or off." Apparently there is an entity out there known as "The Genome".

And then we get into the quoting of author and researcher Victor Albert with no comments or responses from anyone is painful too.

"At least for a plant, junk DNA really is just junk — it's not required." Except that they did not show this - they just showed that one plant can have a small genome and not have a lot of "junk" as they call it, which of course does not really say anything about what "junk" does or does not do in other organisms.

"Nobody's really known what junk DNA does or doesn't do" apparently calling into question the some 10,000 plus papers on the topic.

Apparently, from reading the rest the whole point of this article is that it turns out that people sequenced the genome of a bladderwort and it has a small genome but a lot of genes. Oh and the organism is complex. Therefore, apparently, it follows that

"The findings suggest junk DNA really isn't needed for healthy plants — and that may also hold for other organisms, such as humans."

And this leads us to 'Junk' DNA mystery solved: It's not needed.

So - basically - if ONE FUCKING ORGANISM DELETES SOME OF IT'S NON PROTEIN CODING PORTIONS OF ITS GENOME THEN THIS MEANS THAT ALL NON CODING DNA IS USELESS.

Aaaaaaaaaaaaaaaaaaargh.

And for this evolutionary logic, I am awarding NBC News, Tia Ghose (the author of the piece) and Victor Albert, the 15th coveted Twisted Tree of Life Award.

And two more coming. So proud of the undergrads in my lab who did this work and David Coil for coordinating it with help from Jenna Lang and Aaron Darling. Undergrads at UC Davis sequencing genomes of organisms they isolated. So cool.

That comes to 16.6% if you count all listed. If you exclude session chairs the numbers are a little different but still pretty low.Certainly this does not prove any bias on the part of the meeting organizers. But it certainly suggests to me they might want to think about why the ratio is skewed.

Wednesday, May 08, 2013

Good to see some more papers in microbiology & genomics and related topics going to the preprint server arXiv.

If you are interested in population and evolutionary genetics a good place to keep up with papers on this topic in arXiv is Haldane's Sieve. The good folks there in essence make a separate post about each paper of interest and then people can comment there on the papers, since the commenting functions at arXiv are, well, challenged.

Wednesday, May 01, 2013

Monday I gave a talk for the SMBE Eukaryotic Omics satellite meeting that has been going on at UC Davis. When Holly Bik, a post doc in my lab asked me to talk at the meeting, I said, basically "Well, OK, but I don't really do much work on eukaryotes." And then I came up with an idea - I could make my talk about how it might be good to have a better phylogenetic sampling of eukaryotic genome sequences. I have been a bit obsessed for many many years about phylogenetic sampling of genomes and, well, though I have avoided eukaryotes mostly in most of my genome sequencing work, I figured, I should still get on my soap box about how phylogenetic sampling is a good thing. So, well, I did. And I think we (i.e., the scientific community) really needs a better sampling of eukaryotic genomes.

I have posted my talk to Slideshare and I recorded audio of my talk in synch with the slides and posted that to Youtube. These are below.

I hereby am calling for those people interested in participating in such a phylogeny driven genomic encyclopedia of eukaryotes to make yourselves known. We NEED to do this.

This is really cool: Dr. Eleanor's Book of Common Ants. Free to download. With incredible pics from Alex Wild. And based in part on data from the School of Ants citizen science project. You can download the PDF or the iBook from iTunes. From the folks at "Your Wild Life" including Holly Menninger and Rob Dunn and others. Definitely worth checking out.